EP1485363A1 - Amide cyclique - Google Patents

Amide cyclique

Info

Publication number: EP1485363A1
Authority: EP; European Patent Office
Prior art keywords: formula; compounds; mar; mhet; oxo
Prior art date: 2002-03-12
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Granted

Application number

EP03708178A

Other languages

German (de)

English (en)

Other versions

EP1485363B1 (fr

Inventor

Oliver Schadt

Joachim Leibrock

Helmut Pruecher

Christoph Seyfried

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Merck Patent GmbH

Original Assignee

Merck Patent GmbH

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-03-12

Filing date

2003-03-05

Publication date

2004-12-15

2003-03-05 Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH

2003-03-05 Priority to SI200331440T priority Critical patent/SI1485363T1/sl

2004-12-15 Publication of EP1485363A1 publication Critical patent/EP1485363A1/fr

2008-10-08 Application granted granted Critical

2008-10-08 Publication of EP1485363B1 publication Critical patent/EP1485363B1/fr

2008-12-30 Priority to CY20081101501T priority patent/CY1108674T1/el

2023-03-05 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

150000003950 cyclic amides Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 189
150000003839 salts Chemical class 0.000 claims abstract description 62
239000012453 solvate Substances 0.000 claims abstract description 52
239000000203 mixture Substances 0.000 claims abstract description 45
206010008118 cerebral infarction Diseases 0.000 claims abstract description 15
208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 12
230000004770 neurodegeneration Effects 0.000 claims abstract description 10
208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 10
201000000980 schizophrenia Diseases 0.000 claims abstract description 10
208000018737 Parkinson disease Diseases 0.000 claims abstract description 9
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 8
206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 8
208000023105 Huntington disease Diseases 0.000 claims abstract description 8
208000028017 Psychotic disease Diseases 0.000 claims abstract description 8
206010015037 epilepsy Diseases 0.000 claims abstract description 8
230000007574 infarction Effects 0.000 claims abstract description 8
239000003194 amino acid receptor blocking agent Substances 0.000 claims abstract description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 73
125000000217 alkyl group Chemical group 0.000 claims description 33
229910052760 oxygen Inorganic materials 0.000 claims description 26
125000000753 cycloalkyl group Chemical group 0.000 claims description 24
229910052717 sulfur Inorganic materials 0.000 claims description 24
101100134925 Gallus gallus COR6 gene Proteins 0.000 claims description 22
125000003545 alkoxy group Chemical group 0.000 claims description 20
238000000034 method Methods 0.000 claims description 20
229910052801 chlorine Inorganic materials 0.000 claims description 18
229910052794 bromium Inorganic materials 0.000 claims description 17
229910052740 iodine Inorganic materials 0.000 claims description 17
229910021645 metal ion Inorganic materials 0.000 claims description 16
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 15
229910052731 fluorine Inorganic materials 0.000 claims description 14
239000003814 drug Substances 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 10
230000008569 process Effects 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 8
239000007788 liquid Substances 0.000 claims description 8
239000000825 pharmaceutical preparation Substances 0.000 claims description 8
201000006474 Brain Ischemia Diseases 0.000 claims description 7
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 6
239000000546 pharmaceutical excipient Substances 0.000 claims description 6
239000007787 solid Substances 0.000 claims description 6
SHUHQYGWCDZWAL-UHFFFAOYSA-N 3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C1=CC(F)=CC=C1CC1CCN(CCC(=O)NC=2C=C3OC(=O)NC3=CC=2)CC1 SHUHQYGWCDZWAL-UHFFFAOYSA-N 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
206010012289 Dementia Diseases 0.000 claims description 4
239000002552 dosage form Substances 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
VJZKUKWEDKLXSG-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C=1C=C2NC(=O)OC2=CC=1NC(=O)C(C)N(CC1)CCN1CC1=CC=CC=C1 VJZKUKWEDKLXSG-UHFFFAOYSA-N 0.000 claims description 3
VPGAIUOGXJCGBO-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-n-(2-oxo-3h-1,3-benzoxazol-6-yl)acetamide Chemical compound C=1C=C2NC(=O)OC2=CC=1NC(=O)CN(CC1)CCC1CC1=CC=CC=C1 VPGAIUOGXJCGBO-UHFFFAOYSA-N 0.000 claims description 3
JTJBDTRJKGPUDH-UHFFFAOYSA-N 2-[4-(4-fluorophenoxy)piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)-2-phenylacetamide Chemical compound C1=CC(F)=CC=C1OC1CCN(C(C(=O)NC=2C=C3OC(=O)NC3=CC=2)C=2C=CC=CC=2)CC1 JTJBDTRJKGPUDH-UHFFFAOYSA-N 0.000 claims description 3
FDDJCQUMJNIAMW-UHFFFAOYSA-N 2-[4-(4-fluorophenoxy)piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C=1C=C2NC(=O)OC2=CC=1NC(=O)C(C)N(CC1)CCC1OC1=CC=C(F)C=C1 FDDJCQUMJNIAMW-UHFFFAOYSA-N 0.000 claims description 3
JXMAFIMMLDUUHZ-UHFFFAOYSA-N 2-[4-[(2,4-difluorophenyl)methyl]piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C=1C=C2NC(=O)OC2=CC=1NC(=O)C(C)N(CC1)CCC1CC1=CC=C(F)C=C1F JXMAFIMMLDUUHZ-UHFFFAOYSA-N 0.000 claims description 3
WBJNIUKQZYZFJW-UHFFFAOYSA-N 2-[4-[(3,5-difluorophenyl)methyl]-4-hydroxypiperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C=1C=C2NC(=O)OC2=CC=1NC(=O)C(C)N(CC1)CCC1(O)CC1=CC(F)=CC(F)=C1 WBJNIUKQZYZFJW-UHFFFAOYSA-N 0.000 claims description 3
CKRFXTAVALMBMP-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]-4-hydroxypiperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)acetamide Chemical compound C1CN(CC(=O)NC=2C=C3OC(=O)NC3=CC=2)CCC1(O)CC1=CC=C(F)C=C1 CKRFXTAVALMBMP-UHFFFAOYSA-N 0.000 claims description 3
FAFSKKDUNBEDKB-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]-4-hydroxypiperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C=1C=C2NC(=O)OC2=CC=1NC(=O)C(C)N(CC1)CCC1(O)CC1=CC=C(F)C=C1 FAFSKKDUNBEDKB-UHFFFAOYSA-N 0.000 claims description 3
QMFWLDKGGWVIET-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)-2-phenylacetamide Chemical compound C1=CC(F)=CC=C1CC1CCN(C(C(=O)NC=2C=C3OC(=O)NC3=CC=2)C=2C=CC=CC=2)CC1 QMFWLDKGGWVIET-UHFFFAOYSA-N 0.000 claims description 3
YENJFWJTOPQCQS-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)acetamide Chemical compound C1=CC(F)=CC=C1CC1CCN(CC(=O)NC=2C=C3OC(=O)NC3=CC=2)CC1 YENJFWJTOPQCQS-UHFFFAOYSA-N 0.000 claims description 3
SDEATIKBLQOUCH-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C=1C=C2NC(=O)OC2=CC=1NC(=O)C(C)N(CC1)CCC1CC1=CC=C(F)C=C1 SDEATIKBLQOUCH-UHFFFAOYSA-N 0.000 claims description 3
PAEICXUVEDAGJH-UHFFFAOYSA-N 3-[4-[(4-methoxyphenyl)methyl]piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C1=CC(OC)=CC=C1CC1CCN(CCC(=O)NC=2C=C3OC(=O)NC3=CC=2)CC1 PAEICXUVEDAGJH-UHFFFAOYSA-N 0.000 claims description 3
SZTBXRQJRMWEBD-UHFFFAOYSA-N 3-[4-[(4-methylphenyl)methyl]piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C1=CC(C)=CC=C1CC1CCN(CCC(=O)NC=2C=C3OC(=O)NC3=CC=2)CC1 SZTBXRQJRMWEBD-UHFFFAOYSA-N 0.000 claims description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 claims description 3
XAKXQKCXRZFRAF-UHFFFAOYSA-N n-(2,3-dihydro-1,3-benzoxazol-6-yl)-2-[4-(4-fluorophenyl)butyl-methylamino]acetamide Chemical compound C=1C=C2NCOC2=CC=1NC(=O)CN(C)CCCCC1=CC=C(F)C=C1 XAKXQKCXRZFRAF-UHFFFAOYSA-N 0.000 claims description 3
KXSNTCAIBUSREV-UHFFFAOYSA-N n-(2-oxo-3h-1,3-benzoxazol-6-yl)-2-[4-(thiophen-2-ylmethyl)piperidin-1-yl]acetamide Chemical compound C=1C=C2NC(=O)OC2=CC=1NC(=O)CN(CC1)CCC1CC1=CC=CS1 KXSNTCAIBUSREV-UHFFFAOYSA-N 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
238000011321 prophylaxis Methods 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
JLJZLVHUVHVZPX-UHFFFAOYSA-N 2-[4-(4-fluorophenyl)butylamino]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)acetamide Chemical compound C1=CC(F)=CC=C1CCCCNCC(=O)NC1=CC=C(NC(=O)O2)C2=C1 JLJZLVHUVHVZPX-UHFFFAOYSA-N 0.000 claims description 2
IYCILJDEGFAZLU-UHFFFAOYSA-N 3-[4-(1,3-benzodioxol-5-ylmethyl)piperidin-1-yl]-n-(2-oxo-3h-1,3-benzoxazol-6-yl)propanamide Chemical compound C1=C2NC(=O)OC2=CC(NC(CCN2CCC(CC=3C=C4OCOC4=CC=3)CC2)=O)=C1 IYCILJDEGFAZLU-UHFFFAOYSA-N 0.000 claims description 2
208000019901 Anxiety disease Diseases 0.000 claims description 2
208000028698 Cognitive impairment Diseases 0.000 claims description 2
102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 claims description 2
108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 claims description 2
206010057852 Nicotine dependence Diseases 0.000 claims description 2
208000025569 Tobacco Use disease Diseases 0.000 claims description 2
208000000323 Tourette Syndrome Diseases 0.000 claims description 2
208000016620 Tourette disease Diseases 0.000 claims description 2
230000036506 anxiety Effects 0.000 claims description 2
208000010877 cognitive disease Diseases 0.000 claims description 2
239000003112 inhibitor Substances 0.000 claims description 2
210000004558 lewy body Anatomy 0.000 claims description 2
GOYKQHQUFKLYOS-UHFFFAOYSA-N n-(5-chloro-2-oxo-3h-1,3-benzoxazol-6-yl)-3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propanamide Chemical compound C1=CC(F)=CC=C1CC1CCN(CCC(=O)NC=2C(=CC=3NC(=O)OC=3C=2)Cl)CC1 GOYKQHQUFKLYOS-UHFFFAOYSA-N 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 6
125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 2
201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims 1
125000002619 bicyclic group Chemical group 0.000 claims 1
125000002618 bicyclic heterocycle group Chemical group 0.000 claims 1
206010027175 memory impairment Diseases 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
-1 alkylene radical Chemical class 0.000 description 62
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
150000003254 radicals Chemical class 0.000 description 31
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 24
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
239000007858 starting material Substances 0.000 description 18
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 17
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101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 16
101150035983 str1 gene Proteins 0.000 description 16
239000002904 solvent Substances 0.000 description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
239000004480 active ingredient Substances 0.000 description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
102000038100 NR2 subfamily Human genes 0.000 description 10
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000007795 chemical reaction product Substances 0.000 description 10
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
150000007530 organic bases Chemical class 0.000 description 9
UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 description 8
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 8
102000014649 NMDA glutamate receptor activity proteins Human genes 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
229910052736 halogen Inorganic materials 0.000 description 8
229960003998 ifenprodil Drugs 0.000 description 8
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 8
239000003826 tablet Substances 0.000 description 8
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
150000002367 halogens Chemical class 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000007921 spray Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
238000007792 addition Methods 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
229910052784 alkaline earth metal Inorganic materials 0.000 description 5
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
239000002775 capsule Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
238000003756 stirring Methods 0.000 description 5
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VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000013543 active substance Substances 0.000 description 4
150000001342 alkaline earth metals Chemical class 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000001816 cooling Methods 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000007789 gas Substances 0.000 description 4
229930195733 hydrocarbon Natural products 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
229920000768 polyamine Polymers 0.000 description 4
238000000746 purification Methods 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
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235000013343 vitamin Nutrition 0.000 description 1
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239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
Veterinary Medicine (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Addiction (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

EP03708178A 2002-03-12 2003-03-05 Amide cyclique Expired - Lifetime EP1485363B1 (fr)

Priority Applications (2)

Application Number	Priority Date	Filing Date	Title
SI200331440T SI1485363T1 (sl)	2002-03-12	2003-03-05	Cikliäśni amidi
CY20081101501T CY1108674T1 (el)	2002-03-12	2008-12-30	Κυκλικα αμιδια

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE10210779A DE10210779A1 (de)	2002-03-12	2002-03-12	Cyclische Amide
DE10210779		2002-03-12
PCT/EP2003/002224 WO2003076420A1 (fr)	2002-03-12	2003-03-05	Amide cyclique

Publications (2)

Publication Number	Publication Date
EP1485363A1 true EP1485363A1 (fr)	2004-12-15
EP1485363B1 EP1485363B1 (fr)	2008-10-08

Family

ID=27797699

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
EP03708178A Expired - Lifetime EP1485363B1 (fr)	2002-03-12	2003-03-05	Amide cyclique

Country Status (16)

Country	Link
US (1)	US7816376B2 (fr)
EP (1)	EP1485363B1 (fr)
JP (1)	JP2005519953A (fr)
CN (1)	CN1642927A (fr)
AT (1)	ATE410418T1 (fr)
AU (1)	AU2003212305B2 (fr)
CA (1)	CA2478945A1 (fr)
CY (1)	CY1108674T1 (fr)
DE (2)	DE10210779A1 (fr)
DK (1)	DK1485363T3 (fr)
ES (1)	ES2315483T3 (fr)
PL (1)	PL371215A1 (fr)
PT (1)	PT1485363E (fr)
RU (1)	RU2004130426A (fr)
SI (1)	SI1485363T1 (fr)
WO (1)	WO2003076420A1 (fr)

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US9045459B2 (en)	2010-08-13	2015-06-02	AbbVie Deutschland GmbH & Co. KG	Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy
US9309200B2 (en)	2011-05-12	2016-04-12	AbbVie Deutschland GmbH & Co. KG	Benzazepine derivatives, pharmaceutical compositions containing them, and their use in therapy
US8853196B2 (en)	2011-08-05	2014-10-07	AbbVie Deutschland GmbH & Co. KG	Aminochromane, aminothiochromane and amino-1,2,3,4-tetrahydroquinoline derivatives, pharmaceutical compositions containing them, and their use in therapy
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US9365512B2 (en)	2012-02-13	2016-06-14	AbbVie Deutschland GmbH & Co. KG	Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy
RU2629936C2 (ru) *	2012-05-21	2017-09-05	Др. Аугуст Вольфф Гмбх Унд Ко. Кг Арцнаймиттель	Новые 1,3-бензоксазол-2(3н)-оны и их применение в качестве лекарственных препаратов и косметических средств
US9656955B2 (en)	2013-03-15	2017-05-23	Abbvie Inc.	Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy
US9650334B2 (en)	2013-03-15	2017-05-16	Abbvie Inc.	Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy
KR102237887B1 (ko)	2013-03-15	2021-04-07	멜린타 서브시디어리 코프.	항생제를 사용하여 과체중 및 비만 환자에서 감염을 치료하는 방법
CN104211635A (zh) *	2013-06-03	2014-12-17	中国科学院上海药物研究所	一类哌啶类化合物及其制备方法、药物组合物和用途
MX2016004936A (es)	2013-10-17	2016-12-20	Abbvie Deutschland	Derivados de aminocromano, aminotiocromano y amino-1,2,3,4-tetrahi droquinilina, composiciones farmaceuticas que los contienen, y su uso en terapia.
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2002
- 2002-03-12 DE DE10210779A patent/DE10210779A1/de not_active Withdrawn
2003
- 2003-03-05 US US10/507,581 patent/US7816376B2/en not_active Expired - Fee Related
- 2003-03-05 AT AT03708178T patent/ATE410418T1/de not_active IP Right Cessation
- 2003-03-05 SI SI200331440T patent/SI1485363T1/sl unknown
- 2003-03-05 JP JP2003574639A patent/JP2005519953A/ja active Pending
- 2003-03-05 CA CA002478945A patent/CA2478945A1/fr not_active Abandoned
- 2003-03-05 ES ES03708178T patent/ES2315483T3/es not_active Expired - Lifetime
- 2003-03-05 DK DK03708178T patent/DK1485363T3/da active
- 2003-03-05 DE DE50310609T patent/DE50310609D1/de not_active Expired - Lifetime
- 2003-03-05 PT PT03708178T patent/PT1485363E/pt unknown
- 2003-03-05 AU AU2003212305A patent/AU2003212305B2/en not_active Ceased
- 2003-03-05 PL PL03371215A patent/PL371215A1/xx unknown
- 2003-03-05 CN CNA038057905A patent/CN1642927A/zh active Pending
- 2003-03-05 WO PCT/EP2003/002224 patent/WO2003076420A1/fr not_active Ceased
- 2003-03-05 EP EP03708178A patent/EP1485363B1/fr not_active Expired - Lifetime
- 2003-03-05 RU RU2004130426/04A patent/RU2004130426A/ru not_active Application Discontinuation
2008
- 2008-12-30 CY CY20081101501T patent/CY1108674T1/el unknown

Also Published As

Publication number	Publication date
RU2004130426A (ru)	2005-05-27
WO2003076420A1 (fr)	2003-09-18
DE50310609D1 (de)	2008-11-20
PL371215A1 (en)	2005-06-13
ATE410418T1 (de)	2008-10-15
DE10210779A1 (de)	2003-10-09
AU2003212305B2 (en)	2009-04-23
AU2003212305A1 (en)	2003-09-22
DK1485363T3 (da)	2009-02-02
CA2478945A1 (fr)	2003-09-18
ES2315483T3 (es)	2009-04-01
PT1485363E (pt)	2009-01-09
EP1485363B1 (fr)	2008-10-08
CN1642927A (zh)	2005-07-20
SI1485363T1 (sl)	2009-02-28
US20050124627A1 (en)	2005-06-09
US7816376B2 (en)	2010-10-19
CY1108674T1 (el)	2014-04-09
JP2005519953A (ja)	2005-07-07

Publication	Publication Date	Title
EP1485363B1 (fr)	2008-10-08	Amide cyclique
EP1497279B1 (fr)	2011-03-09	Indoles substitues et leur utilisation comme inhibiteurs de recapture 5ht et comme ligands 5ht
EP0710657B1 (fr)	1998-08-26	Antagonistes des récepteurs d'adhésion
EP0648767B1 (fr)	1997-05-28	Dérivés de piperidine et piperazine qui puissent agir sur le "CNS"
JP5416696B2 (ja)	2014-02-12	オキサジアゾール誘導体およびそれらの代謝型グルタミン酸受容体増強剤としての使用
DE60312998T2 (de)	2007-12-13	1-amido-4-phenyl-4-benzyloxymethyl-piperidin derivative und verwandte verbindungen als neurokinin-1 (nk-1) antagonsisten zur behandlung von erbrechen, depressionen, angstzustände und husten
EP0300272B1 (fr)	1992-09-16	Oxazolidinones
EP0736525B1 (fr)	2000-07-12	Benzonitriles comme 5-HT agonistes et antagonistes
DE4332384A1 (de)	1995-03-30	Adhäsionsrezeptor-Antagonisten III
EP0707006A1 (fr)	1996-04-17	Dérivés d'aroyl-pipéridine
EP3634958A1 (fr)	2020-04-15	Agonistes du récepteur 2 du peptide formylé et agonistes du récepteur 1 du peptide formylé à base de cyclopropyle d'urée
EP0769007A1 (fr)	1997-04-23	Derives de 2-ureido-benzamide
EP1068202A1 (fr)	2001-01-17	1-(3-heteroarylpropyl- ou -prop-2-enyl)-4-benzylpiperidines utilisees comme antagonistes du recepteur de nmda
EP0635505B1 (fr)	1997-10-15	Dérivés de 4-aryloxy et 4-arylthio-piperidine
EP1124824B1 (fr)	2007-08-22	Derives de chromenone et de chromanone utilises comme inhibiteurs d'integrine
EP1572646A1 (fr)	2005-09-14	Composés de n-(indolethyl-)cycloamine
DE19604388A1 (de)	1997-08-14	Arylalkyl-diazinone
DE4429461A1 (de)	1996-02-22	Adhäsionsrezeptor-Antagonisten
DE19602505A1 (de)	1997-07-31	1-(Pyrazol-4-Indol-3-yl)-Piperidine
SK53699A3 (en)	2000-03-13	6-{3-[4-(fluorobenzyle)-piperidine-1-yl]-propionyl}-3h- -benzoxazole-2-one, method for its preparation, its use and pharmaceutical composition containing the same
DE68913167T2 (de)	1994-09-01	Indol-Derivate, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Präparate.
EP0763535A1 (fr)	1997-03-19	Dérivés de pipéridinylméthyloxazolidin-2-one, leur préparation et leur utilisation comme composés pharmacologiques actifs sur le système nerveux central
EP1237877B1 (fr)	2005-07-27	Derive de benzimidazole substitues par carboxamide, leur procede de production et leur utilisation comme medicaments
EP1572685B1 (fr)	2007-01-03	Benzodioxepines substituees
EP1220845B1 (fr)	2003-08-13	Derives de benzimidazole portant comme substituant un arylsulfonamide et leur utilisation comme inhibiteurs de la tryptase

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